Convergence of Accelerated Brain Volume Decline in Normal Aging and Alzheimer's Disease Pathology

Age represents the largest risk factor for Alzheimer's disease (AD) but is typically treated as a covariate. Still, there are similarities between brain regions affected in AD and those showing accelerated decline in normal aging, suggesting that the distinction between the two might fall on a spectrum.

Our goal was to identify regions showing accelerated atrophy across the brain and investigate whether these overlapped with regions involved in AD or where related to amyloid.

We used a longitudinal sample of 137 healthy older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), who underwent magnetic resonance imaging (MRI). In addition, a total of 79 participants also had longitudinal positron emission tomography (PET) data. We computed linear-mixed effects models for brain regions declining faster than the average to investigate variability in the rate of change.

23 regions displayed a 0.5 standard deviation (SD) above average decline over 2 years. Of these, 52% overlapped with regions showing similar decline in a matched AD sample. Beyond this, the left precuneus, right superior frontal, transverse temporal, and superior temporal sulcus showed accelerated decline. Lastly, atrophy in the precuneus was associated with increased amyloid load.

Accelerated decline in normal aging might contribute to the detection of early signs of AD among healthy individuals.